181 research outputs found

    Outcomes of Naviculectomy for Severe Recurrent Clubfoot Deformity

    Get PDF
    Background: Naviculectomy was originally described for resistant congenital vertical talus deformity but was later expanded to use in rigid cavus deformity. This study reviews the operative outcomes of complete excision of the navicular for recurrent deformity in the talipes equinovarus (TEV) population. Methods: After institutional review board approval, all patients undergoing naviculectomy at a single institution were identified. Clinical, radiographic, and pedobarographic data (minimum 2 years’ follow-up) were reviewed. Results: Twelve patients (14 feet) with TEV from 1984 to 2019 were included. All feet had minimum 1 prior operative intervention on the affected foot (mean age = 4.0 years, range 0.2-14.5), with 8/14 having at least 3 prior operative procedures. Complete navicular excision with concomitant procedures was performed in all patients (mean age = 11.7 years, range 5.5-16.1). Mean clinical follow-up from naviculectomy was 5.1 years (range, 2.2-11.2). During follow-up, 6 patients required subsequent surgery, most often secondary to pain and progressive deformity. One patient underwent elective below-knee amputation of the affected extremity. Of the remaining 11 patients, 7 of 11 reported continued pain and 8 of 11 maintained adequate range of motion at the ankle at the most recent follow-up. Conclusion: Clinical follow-up demonstrated deteriorating results in a large percentage of patients. The high rate of additional procedures and continued pain in the current series suggests that even as a salvage procedure, naviculectomy may not provide adequate results for patients. Level of Evidence: Level IV, case series

    Pharmacokinetics, absorption, distribution, metabolism and excretion of the MEK inhibitor zapnometinib in rats

    Get PDF
    Zapnometinib is a MEK inhibitor currently under clinical development for the treatment of COVID-19 and influenza. Zapnometinib has both antiviral and immunomodulatory effects. Information concerning the absorption, distribution, metabolism, and excretion of the compound following single oral doses of 30 mg/kg [14C]-zapnometinib to rats was required to support pharmacology and toxicology studies in animals and clinical studies in man. As part of the development and safety assessment of this substance, zapnometinib was radioactively labeled and used for the investigation of time-dependent plasma concentrations, the rates and routes of excretion, the extent and time-course of compound distribution in body tissues, the metabolite profiles in plasma, urine and feces and the chemical nature of its metabolites. The present study reveals a rapid but low absorption of zapnometinib from the gastrointestinal tract, with more than 90% of the compound being excreted within 48 h, mainly via feces. Whole body autoradiography confirms that zapnometinib was rapidly and widely distributed, with greatest concentrations in the circulatory and visceral tissues. Maximum plasma and tissue concentrations occurred between two and 8 h post dose. Penetration into the brain was low, and elimination from most tissues almost complete after 168 h. Metabolic profiles showed that the main clearance routes were metabolism via oxidative reactions and glucuronidation. These results further strengthen the knowledge of zapnometinib with respect to the clinical development of the drug

    Complete Genome Sequences of Paenibacillus Larvae Phages BN12, Dragolir, Kiel007, Leyra, Likha, Pagassa, PBL1c, and Tadhana

    Get PDF
    We present here the complete genomes of eight phages that infect Paenibacillus larvae, the causative agent of American foulbrood in honeybees. Phage PBL1c was originally isolated in 1984 from a P. larvae lysogen, while the remaining phages were isolated in 2014 from bee debris, honeycomb, and lysogens from three states in the USA

    Figurational Dynamics and Parliamentary Discourses of Living Standards in Ireland

    Get PDF
    While the concept of living standards remains central to political debate, it has become marginal in sociological research compared to the burgeoning attention given to the topic of consumer culture in recent decades. However, they both concern how one does and should consume, and, indeed, behave at particular times. I use the theories of Norbert Elias to explain the unplanned but structured (ordered) changes in expected standards of living over time. This figurational approach is compared to other alternative explanations, particularly those advanced by Bourdieu, Veblen and Baudrillard. Though these offer some parallels with Elias’s theories, I argue that consumption standards are produced and transformed through the changing dependencies and power relations between social classes. They cannot be reduced to the intentions, interests or ambitions of particular elites, nor to the needs of social systems. Using qualitative data from parliamentary debates in Ireland to trace changing norms and ideals of consumption, as well as historical data to reconstruct shifts in social interdependencies, I further contend that discourses of living standards and luxury are vital aspects of the growing identification and empathy between classes, which in turn encourages greater global integration in the face of emigration and national decline

    Immigration and the Common Profit: Native Cloth Workers, Flemish Exiles, and Royal Policy in Fourteenth-Century London

    Get PDF
    Drawing on a wide variety of published and unpublished sources, this article reconstructs a crucial episode in the relationship between the English Crown, its native subjects and the kingdom’s immigrant population during the later Middle Ages. Determined that their presence would boost the development of the local textile industries, Edward III encouraged high numbers of skilled Flemish cloth workers who had been exiled from their home county at the start of the 1350s to settle in the realm. Most of them took up residence in London, where they produced higher-quality cloth for the domestic market and, probably, for export. Soon, however, the immigrants’ activities conflicted with the privileges that had structured the capital’s economic life for centuries. Their work was contested by London’s native weavers who, since the middle of the twelfth century, had enjoyed the sole right to produce cloth in the city. Hoping that the control over the immigrants’ activities would help them to overcome the crisis in the market for lower-quality textiles they were struggling with, the natives petitioned the king to obtain the incorporation of the Flemish weavers into their guild for over twenty-five years. Yet, arguing that the Flemings’ contribution benefited the common profit of the whole kingdom in a way that transcended the interests of any particular group, the Crown rejected all their requests and avoided every attempt at discussion. Each time political communication broke down, the native weavers took out their frustrations by physically attacking their Flemish counterparts. These incidents became increasingly violent during the years leading up to the Peasants’ Revolt in 1381 and came to a dramatic conclusion during the rebellion itself

    The relationship between sensory sensitivity and autistic traits in the general population.

    Get PDF
    Individuals with Autism Spectrum Disorders (ASDs) tend to have sensory processing difficulties (Baranek et al. in J Child Psychol Psychiatry 47:591–601, 2006). These difficulties include over- and under-responsiveness to sensory stimuli, and problems modulating sensory input (Ben-Sasson et al. in J Autism Dev Disorders 39:1–11, 2009). As those with ASD exist at the extreme end of a continuum of autistic traits that is also evident in the general population, we investigated the link between ASD and sensory sensitivity in the general population by administering two questionnaires online to 212 adult participants. Results showed a highly significant positive correlation (r = .775, p < .001) between number of autistic traits and the frequency of sensory processing problems. These data suggest a strong link between sensory processing and autistic traits in the general population, which in turn potentially implicates sensory processing problems in social interaction difficulties

    Genome-Wide Association Study Identifies GPC5 as a Novel Genetic Locus Protective against Sudden Cardiac Arrest

    Get PDF
    BACKGROUND:Existing studies indicate a significant genetic component for sudden cardiac arrest (SCA) and genome-wide association studies (GWAS) provide an unbiased approach for identification of novel genes. We performed a GWAS to identify genetic determinants of SCA. METHODOLOGY/PRINCIPAL FINDINGS:We used a case-control design within the ongoing Oregon Sudden Unexpected Death Study (Oregon-SUDS). Cases (n = 424) were SCAs with coronary artery disease (CAD) among residents of Portland, OR (2002-07, population approximately 1,000,000) and controls (n = 226) were residents with CAD, but no history of SCA. All subjects were of White-European ancestry and GWAS was performed using Affymetrix 500K/5.0 and 6.0 arrays. High signal markers were genotyped in SCA cases (n = 521) identified from the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) (combined n = 19,611). No SNPs reached genome-wide significance (p<5x10(-8)). SNPs at 6 loci were prioritized for follow-up primarily based on significance of p<10(-4) and proximity to a known gene (CSMD2, GPR37L1, LIN9, B4GALNT3, GPC5, and ZNF592). The minor allele of GPC5 (GLYPICAN 5, rs3864180) was associated with a lower risk of SCA in Oregon-SUDS, an effect that was also observed in ARIC/CHS whites (p<0.05) and blacks (p<0.04). In a combined Cox proportional hazards model analysis that adjusted for race, the minor allele exhibited a hazard ratio of 0.85 (95% CI 0.74 to 0.98; p<0.01). CONCLUSIONS/SIGNIFICANCE:A novel genetic locus for SCA, GPC5, was identified from Oregon-SUDS and successfully validated in the ARIC and CHS cohorts. Three other members of the Glypican family have been previously implicated in human disease, including cardiac conditions. The mechanism of this specific association requires further study
    • …
    corecore